Introduction: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20–30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. Aim: To construct and evaluate a preoperative diagnostic method to predict OCLNM in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. Methods: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA), and survival analysis. Results: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881–0.975), 0.878 (95% CI: 0.766–0.990), 0.796 (95% CI: 0.666–0.927), and 0.834 (95% CI: 0.721–0.947) in the training, test, external validation set1, and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. Conclusion: The proposed MRI-based Resnet50 DL model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.
Clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of renal cell carcinoma (RCC) and has a poor 5-year survival rate. In recent years, medical advancement has promoted the understanding of the histopathological and molecular characterization of ccRCC; however, the carcinogenesis and molecular mechanisms of ccRCC remain unclear. Chromatin accessibility is an essential determinant of cellular phenotype. This study aimed to explore the potential role of chromatin accessibility in the development and progression of ccRCC. By the combination of open-access genome-wide chromatin accessibility profiles and gene expression profiles in ccRCC, we obtained a total of 13,474 crucial peaks, corresponding to 5,120 crucial genes and 9,185 differentially expressed genes. Moreover, two potential function modules (P2 and G4) that contained 129 upregulated genes were identified via the weighted gene co-expression network analysis (WGCNA). Furthermore, we obtained five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT), and a prognostic model was established based on these genes through the least absolute shrinkage and selection operator-proportional hazards model (LASSO-Cox) analysis. This model can stratify the ccRCC samples into a high-risk and a low-risk group, from which the patients have distinct prognosis. Further analysis demonstrated a completely different immune cell infiltration pattern between these two risk groups. This study also suggested that mast cell resting is associated with the prognosis of ccRCC and could be a target of immunotherapy. Overall, this study indicated that chromatin accessibility plays an essential role in ccRCC. The five prognostic chromatin accessibility biomarkers and the prognostic immune cells can provide a new direction for the treatment of ccRCC.
Mast cells play complex and context‐dependent roles within the tumor microenvironment, yet their molecular characteristics and functional diversity across human cancers remain poorly defined. In this study, single‐cell RNA sequencing and spatial transcriptomics data are integrated to comprehensively map the transcriptional and spatial heterogeneity of mast cells across ten cancer types. A distinct proinflammatory mast cell (PMC) population is identified, characterized by strong antigen‐presenting features and immune‐activating potential. Mechanistic analyses show that retinoic acid (RA) signaling drives the polarization of PMCs through activation of RARα, which promotes CIITA‐mediated MHC‐II expression, CXCL16 secretion, and T cell recruitment and activation. Across multiple cancer types, tumors with higher PMC abundance are associated with more favorable clinical outcomes. These findings reveal the pivotal role of RA–RARα–CIITA signaling in mast cell reprogramming and suggest that pharmacologic induction of proinflammatory mast cells may represent a promising approach to enhance antitumor immunity.
1 August 2024 in Recent Patents on Anti-Cancer Drug Discovery
Background: Ferroptosis is a new type of programmed apoptosis and plays an important role in tumour inhibition and immunotherapy. Objective: In this study, we aimed to explore the potential role of ferroptosis-related genes (FRGs) and the potential therapeutic targets in oral cavity squamous cell carcinoma (OCSCC). Methods: The transcription data of OCSCC samples were obtained from the Cancer Genome Atlas (TCGA) database as a training dataset. The prognostic FRGs were extracted by univariate Cox regression analysis. Then, we constructed a prognostic model using the least absolute shrinkage and selection operator (LASSO) and Cox analysis to determine the independent prognosis FRGs. Based on this model, risk scores were calculated for the OCSCC samples. The model’s capability was further evaluated by the receiver operating characteristic curve (ROC). Then, we used the GSE41613 dataset as an external validation cohort to confirm the model’s predictive capability. Next, the immune infiltration and somatic mutation analysis were applied. Lastly, single-cell transcriptomic analysis was used to identify the key cells. Results: A total of 12 prognostic FRGs were identified. Eventually, 6 FRGs were screened as independent predictors and a prognostic model was constructed in the training dataset, which significantly stratified OCSCC samples into high-risk and low-risk groups based on overall survival. The external validation of the model using the GSE41613 dataset demonstrated a satisfactory predictive capability for the prognosis of OCSCC. Further analysis revealed that patients in the highrisk group had distinct immune infiltration and somatic mutation patterns from low-risk patients. Mast cell infiltrations were identified as prognostic immune cells and played a role in OCSCC partly through ferroptosis. Conclusion: We successfully constructed a novel 6 FRGs model and identified a prognostic immune cell, which can serve to predict clinical prognoses for OCSCC. Ferroptosis may be a new direction for immunotherapy of OCSCC.
Objective: Buccal mucosa cancer (BMC) is one of the most common oral cancers and has poor prognosis. The study aimed to develop and validate nomograms for predicting the 1‐, 3‐, and 5‐year overall survival (OS) and cancer‐specific survival (CSS) of BMC patients.Methods: We collected and reviewed information on BMC patients diagnosed between 2004 and 2019 from the Surveillance Epidemiology and End Results database. Two nomograms were developed and validated to predict the OS and CSS based on predictors identified by univariate and multivariate Cox regression. An extra external validation was further performed using data from Sun Yat‐sen Memorial Hospital (SYSMH).Results: A total of 3154 BMC patients included in this study were randomly assigned to training and validation groups in a 2:1 ratio. Independent prognostic predictors were identified, confirmed, and fitted into nomograms for OS and CSS, respectively. The C‐indices are 0.767 (Training group OS), 0.801 (Training group CSS), 0.763 (Validation group OS), and 0.781 (Validation group OS), respectively. Moreover, the nomograms exhibited remarkable precision in forecasting and significant clinical significance, as evidenced by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). The final validation using our data from SYSMH also showed high accuracy and substantial clinical benefits within the nomograms. The C‐indices are 0.849 (SYSMH group OS) and 0.916 (SYSMH group CSS). These indexes are better than tumor, node, and metastasis stage based on prediction results.Conclusions: The nomograms developed with great performance predicted 1‐, 3‐, and 5‐year OS and CSS of BMC patients. Use of the nomograms in clinical practices shall bring significant benefits to BMC patients.